1,721,469 research outputs found
Bench-to-bedside review: Appropriate antibiotic therapy in severe sepsis and septic shock--does the dose matter?
Full text linkAppropriate antibiotic therapy in patients with severe sepsis and septic shock should mean prompt achievement and maintenance of optimal exposure at the infection site with broad-spectrum antimicrobial agents administered in a timely manner. Once the causative pathogens have been identified and tested for in vitro susceptibility, subsequent de-escalation of antimicrobial therapy should be applied whenever feasible. The goal of appropriate antibiotic therapy must be pursued resolutely and with continuity, in view of the ongoing explosion of antibiotic-resistant infections that plague the intensive care unit setting and of the continued decrease in new antibiotics emerging. This article provides some principles for the correct handling of antimicrobial dosing regimens in patients with severe sepsis and septic shock, in whom various pathophysiological conditions may significantly alter the pharmacokinetic behaviour of drugs
Nosocomial Pneumonia: Strategies for Management: General Pharmacological Considerations and Dose Adjustment in Antibiotic Therapy for HAP
No full textVoriconazole treatment in invasive candidiasis
No full textAlthough echinocandins are often the preferred front line regimen for uncomplicated Candida bloodstream infections, their penetration into several deep tissue sites, notably the eye and brain, is limited. In these situations, voriconazole can be a useful first line therapy in the treatment of deep-tissue candidiasis involving the eye and CNS, or as a step-down regimen for other complicated infections involving the gastrointestinal tract, heart, lung, and bone
Voriconazole toxicology
No full textTreatment with voriconazole can be associated with a number of adverse effects that in some cases may require treatment discontinuation or switching to another agent. The most common toxicities observed during voriconazole therapy include visual disturbances, neurological side effects, asymptomatic liver injury, and drug interaction s. Occasionally, more severe neurological adverse include hallucinations or encephalitis, especially in patients with high exposures (voriconazole troughs > 5.5 mg/L) have been reported. Severe toxicities, including neuropathy, severe phototoxicity / squamous cell carcinoma, and fluoride toxicity /periostitis, should be anticipated in a subset of patients receiving long-term voricoconazole therapy, especially at high doses
Therapeutic drug monitoring of voriconazole
No full textInvasive fungal diseases are associated with significant morbidity and mortality, especially in immunocompromised patients. Voriconazole is a first-line treatment for invasive aspergillosis, and an effective agent for candidiasis, fusariosis and scedosporiosis. A growing body of evidence suggests that the efficacy and safety of voriconazole is improved through therapeutic drug monitoring (TDM). Herein, we review key pharmacological features of voriconazole that justify TDM in specific populations, and provide recommendations for how TDM is approached in clinical practic
Drug interactions with voriconazole
No full textDrug interactions are a potential problem with voriconazole therapy, due to the antifungal's extensive interaction with human cytochrome P450 enzymes and transporters. While some of these interactions can be severe and result in either undetectable bloodstream concentrations of voriconazole, or possibly toxic levels of the coadministered medication, most interactions can be anticipated and safely managed with the aid of computerized screening databases and therapeutic drug monitoring. In this chapter, we highlight common pharmacokinetic drug-drug interaction s that occur with voriconazole, and discuss strategies for their management
Time to first antibiotic dose for community-acquired pneumonia: a challenging balance
No full textThis is a commentary on the manuscript of Fally et al. focused on the time to first antibiotic dose (TFAD) in patients with community-acquired pneumonia (CAP). The authors analyzed the impact of 4 and 8-h timeframes on several outcomes in a cohort of 2,264 patients with CAP hospitalized at four hospitals in Denmark. After accounting for potential confounders and stratifying patients by the pneumonia severity or the probability to receive early antibiotic therapy, none of the outcomes was affected by the early antibiotic administration.
To place the study in the context, we have revised the history of the debate about TFAD for CAP, mentioning also the evidence for other bacterial infections. Except of septic shock and bacterial meningitis for which literature supports the use of early (<1-3 h) antibiotic initiation, for other less severe conditions the evidence of benefit is missing. On the other hand, to pursue strict TFAD may be associated with adverse events.
We deem the study of Fally et al. underlines that the real challenge in the management of patients suspected of having CAP or other non-severe bacterial infections is to differentiate patients who need to be treated in few hours from those who would not be harmed by withholding antibiotics until the diagnosis of infection is confirmed
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